This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Impaired neurodevelopmental outcome has been observed for survivors of neonatal heart surgery for congenital heart defects. There is prior evidence indicating the importance of preoperative cerebral well-being on the observed outcome. Furthermore, it is well known that the surgical parameters which include cardiac by-pass, deep-cooling and arrest need to be optimized via real-time, bed-side monitoring. A crucial parameter that is largely inaccessible is the cerebral blood flow (CBF). We have recently developed diffuse correlation spectroscopy (DCS) for non-invasive, continuous measurement of relative CBF. In this work, we report our first results from its clinical application to neonates where it was combined with diffuse optical spectroscopy (DOS) for measurement of blood oxygenation and cerebral oxygen metabolism. In this two-cohort study, Neonates with severe congenital heart defects scheduled for cardiac surgery were measured preoperatively to assess cerebral CO2 reactivity and autoregulation. The first cohort (n=44) was measured during an extended period of hypercapnia in the MRI magnet and DCS measurement was validated against arterial spin-labeling MRI measure of CBF showing good agreement between two methods. An impairment of CO2 reactivity was not observed due to large range of CO2 reactivity values reported in the literature and the sample size. The second cohort is now being recruited (n=6) for a more extended monitoring including the preoperative preparation period and statistically comparing the findings with the post-operative outcome measures. Ultimately, we will monitor cerebral well-being during and immediately after cardiac surgery utilizing the power of the optical techniques for bed-side monitoring.